NMR and mass spectrometry methods will be developed in 3 core research projects. Studies in Core 1 will test new 2D NMR and decoupling techniques as well as other methods to develop very high sensitivity. 13/C NMR isotopomer analysis. These methods have fundamental advantages over conventional tracer studies, and as such are broadly applicable to diverse biological questions and animal models. The specific target is to establish protocols for quantitation of fluxes through key pathways involved with gluconeogenesis, glycogenolysis and fatty acid oxidation in the human liver by analysis of 13/C in metabolic products in blood and urine. These procedures have potential for rapid translation to clinical research in numerous institutions. In Core 2 computational methods will be expanded to integrate all forms of 13/C isotopomer data (2D NMR, mass spectroscopy and tandem mass spectrometry), and more complex problems in isotopomer analysis will be investigated. Core 3 will extend our capabilities of monitoring biological cations. Superior 23/Na NMR shift agents and new ligands to monitor divalent cations will be a high priority. The Facility has added a 600 MHz NMR spectrometer in the last few months, and the existing 300 MHs and 500 MHz systems have been upgraded. The Facility will support 5 NMR spectroscopy/imaging systems at two universities. Multiple independent investigators will used the resource in collaborative studies or independent service projects, and dissemination and training activities will continue or be expanded.